With the upcoming EU regulation on the use of in-vitro diagnostic devices, a critical evaluation of the current status of our in-house developed LC-MS/MS methods is timely and of great relevance. Recently, much attention has been devoted to the need for better specification of analytical and clinical performance. Appropriate reporting of the actual achieved analytical performance is an important determinant of the clinical performance and subsequent clinical effectiveness of a test. We advocate for the application of CLSI C62-A guidelines for method validation and suggest some adaptations for analytical validation of in-house developed LC-MS/MS methods for endogenous substances. Additionally, we underline the importance of well-equipped reviewers and standardized method description, including the presentation of figural evidence of obtained method performance. Achieving this ensures future quality of our in-house developed LC-MS/MS methods.